Our progress in the last year is in the line of research that we have been developing in the field of protein-tyrosine kinases. We have recently identified the major tyrosine phosphorylated protein observed after engagement of Fcgamma receptors as p120c-cbl. We had already characterize this protein as an SH3 binding protein, because it specifically associates to the SH3 domains of p47nck. In the myelomonocytic system we have observed that p120c-cbl associates with the SH3 domain of the non-receptor protein-tyrosine kinase p56lyn. In another line of work, we have characterized cbl-b, a new proto-oncogene belonging to the c-cbl family, as an SH3 binding protein. Regulation of the phosphorylation of this protein by SH domain interactions is in progress. Protein-protein interactions have been analyzed in the tyrosine kinases p59fyn and p55fgr by mutational analysis. We have observed that this closely related kinases are very diferently affected by mutations in very conserved residues of their SH2 and SH3 domains, suggesting that these domains regulate through various mechanisms the activity of these enzymes. During this last year we have also identified and characterized a second protein found to specifically associate to p47nck. This gene have been recently cloned by Derry et al. (Cell 78:635-644) and denominated WASP, because it has been found to be mutated in WAS (Wiskott-Aldrich Syndrome) patients. We have characterized the protein expressed by this gene as an SH3 binding protein of 66 kDa, which is present in the nucleus, cytosol and membrane of myelomonocytic cells.